Smooth muscle controller

ABSTRACT

A method of promoting the healing of a lesion in a smooth muscle, comprising selecting a smooth muscle portion having a lesion and applying a non-excitatory electrical field to the portion, which field reduces the mechanical activity of the portion.

FIELD OF THE INVENTION

[0001] The present invention is related to the field of controllingmechanical and/or electrical activity of smooth muscle by applyingelectrical fields to the muscle.

BACKGROUND OF THE INVENTION

[0002] In many body tissues, activity of individual cells, especiallycontraction, is initiated by changes in trans-membrane potentials. Thesetypes of tissue are also called excitable tissue, since when they areexcited by an electrical signal, they react by activation. Some examplesof excitable tissue include: cardiac muscle, skeletal muscle, smoothmuscle and neural tissue. In many cases, the activity of large numbersof such excitable tissue cells is synchronized by propagating electricalactivation signals. An activation signal is an electrical signal which,when it reaches an excitable cell, causes it to depolarize and performits activity. In addition, the depolarization creates a new propagatingactivation signal which then continues to propagate towards the nextun-activated cell. In most excitable tissue, the cell is refractoryafter a depolarization, such that the activation signal cannotimmediately travel backwards.

[0003] The gastrointestinal (GI) tract is an example of a majorphysiological system in which many activities are coordinated bypropagating electrical activation signals. The GI tract comprise astomach, a small intestine and a large intestine. In a typical digestiveprocess, food is chewed in the mouth and enters the stomach fordigestion. The food is periodically passed to the antrum for grindingdown and then passed back to the stomach. After a period of time, thepyloric sphincter opens and the food is passed to the small intestine.In the small intestine the food is churned and passed forward by arhythmic motion of the intestines, until it reaches the large intestine.A one way sphincter allows movement only from the small intestine to thelarge intestine. Once in the large intestine, the food is furtherchurned and compacted by motions of the large intestines. These motionsalso advance the digested food, now feces, to a pair of outletsphincters, which mark the end of the GI tract.

[0004] The GI tract is mostly composed of smooth muscle, which, whendepolarized, contracts. All of the above described movements of the GItract are synchronized by propagating activation signals. As can beappreciated, in many cases, these electrical signals are not properlyactivated and/or responded to, resulting in disease. In one example, anulcer causes inflammation of GI tissue. The inflamed tissue may generatespurious activation signals, which can cause the stomach to contract ina chaotic manner. The inflamed tissue may also affect the activationprofile of the stomach by not conducting activation signals or by havinga different conduction velocity than healthy tissue.

[0005] Pacing the GI tract is well known in the art, for example asshown in U.S. Pat. Nos. 5,292,344 and 5,540,730, the disclosures ofwhich are incorporated herein by reference. The '730 patent describesboth increasing and decreasing the excitability of the GI tract bystimulating different portions of the vagus nerve. The '344 patentdescribes a pacemaker which directly stimulates portions of the GItract. Electrical stimulation of the GI tract is also known to be usedfor stimulating the GI tract of patients suffering from post operativedamping syndrome, as evidenced by SU 1039506, the disclosure of which isincorporated herein by reference.

[0006] The uterus also comprises smooth muscle, which contracts inresponse to electrical activation signals. “Uterine Electromyography: ACritical Review” by D. Devedeux, et al., Am. J. Obstet Gynecol 1993;169:1636-53, the disclosure of which is incorporated herein byreference, describes the different types of uterine muscle andelectrical signals generated by such muscles. An important finding whichis described therein is that electrical activity in the uterus appearsto be uncorrelated prior to labor, but when labor is established, thecontractions and the electrical activity associated to them becomehighly synchronized.

[0007] In current medical practice, labor can be delayed byadministering certain drugs. However the operation of these drugs issomewhat uncertain. In addition, labor can be induced using other drugs,such as Oxytocin. Unfortunately, the dosage of Oxytocin which isrequired cannot be known in advance and overdoses of the drug can resultin over-contraction which can mechanically damage the fetus and/or themother.

[0008] SU 709078, the disclosure of which is incorporated herein byreference, describes stimulating the uterus after labor using anexternally applied electrical current, to increase the contractions andaid in the expulsion of the afterbirth and reduce bleeding by rapidlyshrinking the uterus.

[0009] The use of locally applied electrical fields for reducing pain iswell known in the art. “Electrical Field Stimulation—MeditatedRelaxation of a Rabbit Middle Cerebral Artery”, D. A. Van Ripper and J.A. Bevan, Circulatory Research 1992; 70:1104-1112, the disclosure ofwhich is incorporated herein by reference, describes causing therelaxation of an artery by applying an electric field. U.S. Pat. No.4,537,195, the disclosure of which is incorporated herein by reference,describes treatment of pain using TENS (Transcutaneous Electrical Nervestimulation), for treatment of headaches. It is hypothesized in thispatent that the electrical stimulation prevents the constriction ofarteries by stimulation of the muscle in the walls of the arteries,thereby preventing the dilation of capillaries, which dilation is acause of headaches.

[0010] SU 1147408, the disclosure of which is incorporated herein byreference, describes a method of changing the distribution of blood flowin and about the liver, by applying electrical fields to arteries,varying the frequency of the field in synchrony with the cardiac rhythm.

[0011] U.S. Pat. No. 5,447,526, the disclosure of which is incorporatedherein by reference, describes a transcutaneous electrical smooth musclecontroller for inhibiting or decreasing the contraction of smoothmuscle, especially uterine muscle. The controller, which is applied tothe outside of the abdomen may also sense muscle contractions and effectinhibitory or stimulatory pulses unto the uterus as a whole, dependingon the medical application, in response to sensed contractions.

SUMMARY OF THE INVENTION

[0012] It is an object of some aspects of the present invention toprovide a method of directly and locally controlling the contractionand/or force of contraction of smooth muscles. Such control isespecially employed, in particular preferred embodiments of theinvention, in the gastrointestinal (GI) tract, the uterus, the bladder,endocrine glands, the gall bladder and blood vessels.

[0013] The inventors have found that the force of contraction of asmooth muscle can be both increased and decreased by a judicialapplication of a non-excitatory electric field. A non-excitatoryelectric field is an electric field which does not induce a propagatingaction potential in the smooth muscle. Such a non-excitatory electricfield does, however, modify the reaction of the smooth muscle to anexcitatory field. The inventors have also found that it is possible todesensitize smooth muscle to an activation signal, thereby thedesensitized smooth muscle does not respond to an activation signal andalso does not propagate the activation signal. Shortly after the fieldis removed, its effects are undone. It should be appreciated that manysmooth muscles are characterized by multiple layers of fibers, thefibers in each layer having a preferred orientation. In a preferredembodiment of the invention, individual layers are selectivelycontrolled by applying the electric field to be substantially parallelto the fiber orientation (in which case the field is highly effective).When a lesser degree of interaction between the muscle layer and thefield is desired, the field is preferably applied perpendicular to themuscle fibers.

[0014] It is an object of some embodiments of the present invention toprovide a method of more precisely controlling the GI tract than ispossible using drugs and/or single or multi-site pacing. In a preferredembodiment of the present invention, the force of contraction of aportion of the GI tract is increased, such as to compensated forweakened contraction and/or to advance an otherwise stuck bolus.Alternatively or additionally, the force of contraction may be reduced,such as to treat a patient with overly sensitive intestines.Alternatively or additionally, a section of the intestines may bedesensitized or blocked from electrical activation signals in order topromote the healing of a lesion in the section. Reducing or blockingcontraction is also useful in treating acute diarrhea and to stopleakage from a stoma, when such leakage is undesired. Additionally oralternatively, the activation profile of the GI tract, which normallyincludes a forward moving wave and a returning wave, is changed, forexample, by blocking the returning wave (the reflux), so as to increasethe motility of the intestines. Blocking the returning wave may beperformed by desensitizing one or more segments of the intestines afterthe forward wave has passed, so that the returning wave will be stoppedat the desensitized segment. Alternatively, the entire length of theintestines is desensitized for the duration of the returning wave. Afterthe returning wave is stopped, the desensitizing field is preferablystopped so as to allow the forward wave to properly propagate. Theforward and returning waves can be detected either by their mechanicalactivity or, more preferably, by their electrical activity.

[0015] In a particular preferred embodiment of the present invention,the tension of the lower end of the colon is reduced so as to improvelocal blood supply and aid in the healing of hemorrhoids and analfissures. It has recently been suggested that much of the painassociated with hemorrhoids is caused by ischemia of the tissue, whichin turn, is caused by abnormally increased tension of the lower colon.Such tension has been hereunto been treated using topically applieddrugs, such as nitroglycerin.

[0016] An endoscope, in accordance with another preferred embodiment ofthe present invention, locally controls the activity of the intestinesso as to cause the smooth muscle to advance and/or retreat theendoscope. Alternatively or additionally, local electricaldesensitization is used as a replacement and/or in addition torelaxation of the bowels using drugs.

[0017] Although some of the embodiments of the present invention havebeen described with respect to an endoscope or a colonoscope, theseembodiments of the invention should be understood to apply to invasiveprobes in general and to endoscopes, colonoscopes, hysteroscopes andrectoscopes, in particular.

[0018] It is an object of another preferred embodiment of the presentinvention to provide a method of more precisely controlling labor,including, delaying and/or advancing the onset of labor, increasing ordecreasing the length of labor and/or stopping labor from proceedingafter it has started or when it is still in the pre-labor stages.Stopping labor is especially important for treating cases of pre-termonset of labor. Such control is exerted, in accordance with a preferredembodiment of the invention, by reducing the contractility of theuterine muscles, increasing their contractility or by desensitizing themso that synchronized contractions cannot occur. It is hypothesized thatlabor is a self-feeding process, where increased forces of contractiongenerate even stronger forces of contraction in the next contractioncycle. By damping the contraction force, such a feedback loop can bebroken. In addition, when the uterus is desensitized, contractionscannot occur and labor is at least temporarily stopped, withoutsignificant danger to the fetus, as might be expected from drugs. Laborinterrupted in this way can be rapidly restarted, without the problemsassociated which drug-terminated labor. In a preferred embodiment of theinvention, spurious electrical activation signals arising from anomalousportions of the uterus, such as fibroid containing portions, whichactivation signals may cause premature labor, are reduced by localdesensitizing and/or blocking of the uterine tissue.

[0019] It accordance with another preferred embodiment of the invention,menstruationally meditated contractions of the uterus (cramps) aretreated by detecting such cramps and applying a desensitizing electricalfield to the uterus to damp such cramps. Alternatively, such adesensitizing electric field may be applied during the time when suchcramps may be expected to occur.

[0020] An object of another preferred embodiment of the presentinvention is to control the contractility of the bladder. In onepreferred embodiment of the invention, the bladder is desensitized suchthat it does not spontaneously contract when such contraction isundesirable. Preferably, an apparatus for controlling the bladder inaccordance with a preferred embodiment of the invention, includes afeedback mechanism, which stops its activity when the bladder becomesover full. In an additional or alternative embodiment of the invention,the force of contraction of the bladder is increased during urination.In a preferred embodiment of the invention, the force of contraction ofthe bladder is increased in patients having bladder hypertrophy, so thatthe bladder will gradually shrink. Such treatment is preferably combinedwith drug treatment and/or an implantation of a stent, which treatmentsmay be used to reduce blockage of the urethra.

[0021] In accordance with another preferred embodiment of the invention,the output rate of endocrine or neuro-endocrine glands is controlled,preferably reduced, by applying a desensitizing electric field. In apreferred embodiment of the invention, a desensitizing electric field isapplied to the beta islet cells of the pancreas, so as to reduce insulingeneration in patients suffering from hyper-insulinemia levels.Preferably, such control is applied without measuring the electricalactivity of the beta islet cells. Alternatively or additionally, suchcontrol is applied while monitoring the blood glucose level. Thedesensitizing field is preferably a locally applied DC field, whosepolarity is switched at a very low frequency, such as once an hour, soas to avoid polarization of the electrodes and/or damage to the tissue.

[0022] Another aspect of the present invention relates to treatingvascular spasm, angina pectoris and/or abnormal blood pressure, byelectrically controlling large blood vessels in the body. In accordancewith a preferred embodiment of the invention, large veins, such as theabdominal veins are relaxed by applying a local inhibitory electricfield to them. Alternatively or additionally, large arteries, such asthe aorta, are relaxed by applying a local inhibitory electric field tothem. Alternatively or additionally, excitatory fields are applied tothe arteries and/or veins so as to constrict them. As can beappreciated, changing the volume of the arteries and veins can directlyaffect a patient's blood pressure and/or cardiovascular performance. Inaddition, relaxing the veins reduces the preload to the heart, which canstop an episode of ischemia, e.g., angina pectoris. Further, relaxingthe aorta is useful in cases of vascular spasm, which, in many cases, isthe cause of angina pectoris.

[0023] The relaxing electrical field is preferably applied to the bloodvessels in spasm, which, in some cases, may be coronary blood vessels.Electrically induced relaxation of blood vessels may be used instead ofor in addition to pharmaceuticals. Further, forced relaxation ofarteries and veins is useful for treating an acute ischemic event.Typically, the ischemic event causes increased heart rate which furtherstrains ischemic cardiac tissue. By reducing the preload and/or theafterload of the heart, the cardiac demand is reduced, which reduces theoxygen demand of the ischemic tissues and/or allows better perfusion ofthe ischemic tissues. Additionally or alternatively, the diastole may beextended to aid the perfusion of the cardiac muscle. Extending thediastole may be achieved, for example, by desensitizing at least aportion of the heart, using techniques, such as described in PCTIL97/00012, “Electrical Muscle Controller”, filed on Jan. 8, 1997, thedisclosure of which is incorporated herein by reference.

[0024] There is therefore provided for, in accordance with a preferredembodiment of the invention, a method of promoting the healing of alesion in a smooth muscle, comprising:

[0025] selecting a smooth muscle portion having a lesion; and

[0026] applying a non-excitatory electric field to the portion, whichfield reduces the mechanical activity at the portion.

[0027] Preferably, applying an electric field comprises desensitizingthe smooth muscle portion. Alternatively or additionally, applying anelectric field comprises blocking the electrical activity of smoothmuscle surrounding the lesion.

[0028] Preferably, the lesion is an ischemic portion of the muscle.Alternatively or additionally, the lesion is a sutured portion of themuscle.

[0029] Preferably, reducing the mechanical activity comprises inhibitingmechanical activity at the location.

[0030] In a preferred embodiment of the invention, the smooth muscleportion is part of a gastrointestinal (GI) tract.

[0031] There is also provided in accordance with a preferred with apreferred embodiment of the invention, a method of treating diarrhea,comprising:

[0032] selecting a portion of irritated intestine; and

[0033] applying an electric field to the portion, which field reducesthe mechanical activity at the portion.

[0034] There is also provided in accordance with a preferred embodimentof the invention, a method of treating obesity, comprising:

[0035] selecting at least a portion of a stomach; and

[0036] applying an electric field to the portion, which field delays orprevents the emptying of the stomach.

[0037] There is also provided in accordance with a preferred embodimentof the invention, a method of treating nausea, comprising,

[0038] selecting at least a portion of a stomach; and

[0039] applying an electric field to the portion, which field reducesthe mechanical activity of the stomach.

[0040] There is also provided in accordance with a preferred embodimentof the invention, a method of controlling emptying of a stoma,comprising:

[0041] applying an electric field to an exit portion of the stoma, whichfield reduces the motility of the end portion; and

[0042] removing said field when emptying of the stoma is desired.

[0043] Preferably, the method further comprises applying a secondelectric field to the exit portion, which second field increases themotility of the stoma, when emptying of the stoma is desired. The secondfield may be an excitatory field. Additionally or alternatively, thesecond field is one which increases the force of contraction.

[0044] There is also provided in accordance with a preferred embodimentof the invention, a method of treating a hemorrhoid, comprising:

[0045] providing a patient having a colon; and

[0046] applying an electric field to a portion of the colon, which fieldrelaxes at least a portion of the colon, near an exit therefrom.

[0047] Preferably, the hemorrhoid is not situated at said portion of thecolon. Alternatively or additionally, the method comprises:

[0048] measuring a tension in the portion of the colon,

[0049] wherein applying an electric field comprises applying an electricfield when the measured tension is above a predetermined amount.

[0050] In a preferred embodiment of the invention, in a method adescribed above, applying an electric field comprises applying theelectric field at a delay after a local activation time.

[0051] There is also provided in accordance with a preferred embodimentof the invention, a method of increasing the motility of a GI tract,comprising:

[0052] selecting a portion of the GI tract; and

[0053] applying a non-excitatory electric field to the portion, whichfield increases the force of contraction at the portion.

[0054] Preferably the method includes applying a second electric fieldto a second portion of the GI tract, downstream from said portion, whichsecond electric field decreases the force of contraction at the secondportion.

[0055] There is also provided in accordance with a preferred embodimentof the invention, a method of increasing the motility of a GI tract,comprising:

[0056] determining a timing of a returning wave in the GI tract; and

[0057] applying an electric field to at least a portion of the GI tract,which electric field reduces the response of the GI tract to thereturning wave.

[0058] Preferably, determining a timing comprises detecting a forwardwave and wherein applying an electric field comprises applying anelectric field only at times where it does not substantially interferewith the forward wave.

[0059] Alternatively or additionally, determining a timing comprisesdetecting a returning wave and wherein applying an electric fieldcomprises applying an electric field only at times where itsubstantially interfere with the returning wave.

[0060] Alternatively or additionally, applying an electric fieldcomprises applying an electric field which inhibits the propagation ofan activation signal, which activation signal synchronizes the returningwave.

[0061] Alternatively or additionally, applying an electric fieldcomprises applying an electric field which reduces the force ofcontraction in at least a portion of the GI tract.

[0062] There is also provided in accordance with a preferred embodimentof the invention, a method of selectively exciting only a layer ofmuscle in a smooth muscle having a plurality of muscle layers, each witha different fiber orientation, comprising:

[0063] applying an inhibitory electrical field, parallel to the a fiberorientation of a first layer of muscle, to the muscle; and

[0064] applying an excitatory electric field to the muscle, whichelectrical field excites a second layer of the muscle.

[0065] There is also provided in accordance with a preferred embodimentof the invention, a method of selectively increasing the force ofcontraction of only a layer of muscle in a smooth muscle having aplurality of muscle layers, each with a different fiber orientation,comprising:

[0066] applying an inhibitory electrical field, parallel to the a fiberorientation of a first layer of muscle, to the muscle; and

[0067] applying a second electric field to the muscle, which secondelectric field is oriented parallel to the fiber orientation of a secondlayer of muscle and which second field increases the force ofcontraction in the second layer of muscle.

[0068] There is also provided in accordance with a preferred embodimentof the invention, a method of multi-point pacing for a smooth muscle,comprising:

[0069] applying excitatory electric fields at a plurality of locationson said muscle; and

[0070] applying at least one inhibitory electric field at a secondplurality of locations, situated among said plurality of locations,wherein said inhibitory electric field prevents the propagation of anactivation signal between said first plurality of paced locations.

[0071] There is also provided in accordance with a preferred embodimentof the invention, apparatus for controlling at least the local activityof a portion of an in vivo smooth muscle, comprising:

[0072] a plurality of electrodes, adapted to be in contact with aportion of smooth muscle to be controlled; and

[0073] a controller which electrifies said electrodes with an electricalfield which does not generate a propagating action potential in thesmooth muscle, which electrical field modifies the reaction of thesmooth muscle to an activation signal.

[0074] Preferably, the apparatus includes an electrical activity sensorwhich detects electrical activity at the portion and wherein saidcontroller electrifies said electrodes responsive to signals from saidsensor. Preferably, the controller electrifies each of said electrodesis responsive to its local electrical activity. Additionally oralternatively, the electrical activity sensor senses electrical activitythrough ones of said plurality of electrodes.

[0075] Alternatively or additionally, the apparatus includes animpedance sensor, which senses at least one impedance between selectedones of said plurality of electrodes.

[0076] Alternatively or additionally, the apparatus includes a forcetransducer which detects mechanical activity at the portion and whereinsaid controller electrifies said electrodes responsive to signals fromsaid sensor. Preferably, said controller applies an inhibitory electricfield to the muscle, when said mechanical activity is above a certainthreshold. Alternatively or additionally, the electrification at each ofsaid electrodes is responsive to its local mechanical activity.

[0077] Alternatively or additionally, the non-excitatory field inhibitsmechanical activity at the portion. Alternatively or additionally, thenon-excitatory field reduces the force of contraction at the portion.Alternatively or additionally, the non-excitatory field increases theforce of contraction at the portion. In a preferred embodiment of theinvention, the controller electrifies at least one of said electrodeswith an excitatory electric field.

[0078] In a preferred embodiment of the invention, the plurality ofelectrodes are arranged in a two-dimensional matrix.

[0079] Alternatively or additionally, the controller selectivelyelectrifies ones of said plurality of electrodes to selectively generateone of two perpendicular electric fields.

[0080] In a preferred embodiment of the invention, the controller isadapted to be implanted inside a stomach and attached to the stomachwall.

[0081] Alternatively or additionally, the apparatus is adapted to beimplanted inside a uterus and attached to the uterus wall.

[0082] Alternatively or additionally, the apparatus is adapted to beimplanted inside the body and outside a portion of the GI tract.

[0083] Alternatively or additionally, the apparatus is adapted to beimplanted inside the body and outside a uterus.

[0084] In a preferred embodiment of the invention, where the controlleris adapted for a uterus, the controller determines a frequency ofcontractions in the uterus and wherein said controller electrifies saidelectrodes responsive to said determined frequency.

[0085] Preferably, the electrodes comprise elastic leads.

[0086] In a preferred embodiment of the invention, the electrodes areattached to a plurality of remote regions of said uterus.

[0087] In a preferred embodiment of the invention, the controller sensesand inhibits mechanical activity in substantially the entire uterus.Alternatively or additionally, the controller increases the force ofcontraction in substantially the entire uterus.

[0088] In a preferred embodiment of the invention, the controller is ina capsule adapted to be inserted into a rectum or into a vagina.

[0089] Alternatively or additionally, the electrodes are adapted to beimplanted inside the body while said controller is adapted to besituated outside the body. Preferably, the electrodes are adapted to bedisconnected from said smooth muscle from outside the body.

[0090] There is also provided in accordance with a preferred embodimentof the invention, an anastomosis button comprising:

[0091] a sleeve portion for joining two portions of a GI tract;

[0092] at least two electrodes adapted to be in electrical contact withthe GI tract, at either side of the button; and

[0093] a controller which electrifies the electrodes to reduce the forceof contraction in the GI tract near the button.

[0094] Preferably, the controller transmits a pacing signal from the GItract on one side of the button to the GI tract on the other side of thebutton.

[0095] Alternatively or additionally, reducing the force comprisesinhibiting electrical activity of the GI tract at the button.

[0096] There is also provided in accordance with a preferred embodimentof the invention, apparatus for inhibiting a returning wave in anintestine, comprises:

[0097] at least one electrode for applying an inhibiting electric fieldto a portion of the intestine;

[0098] a sensor which senses the propagation of waves in the intestine;and

[0099] a controller which electrifies said electrode responsive to asensed propagating wave.

[0100] Preferably, the sensor detects the returning wave.

[0101] There is also provided in accordance with a preferred embodimentof the invention, apparatus for advancing a bolus comprising:

[0102] at least one first electrode, for applying an electrical field toa first portion of the GI tract adjacent said bolus;

[0103] at least one second electrode, for applying an electric field toa second portion of the GI tract downstream from said bolus; and

[0104] a controller which electrifies the at least one first electrodewith a non-excitatory field which increases the force of contraction atthe first portion and which electrifies the at least one secondelectrode with a non-excitatory electric field which relaxes the muscleat the second portion.

[0105] Preferably, the apparatus comprises an impedance sensor fordetecting the existence of a bolus at the first portion of the GI tract.

[0106] There is also provided in accordance with a preferred embodimentof the invention, a method of aiding the examination of a GI tract,comprising:

[0107] providing an elongated probe, having a tip, inside a portion of aGI tract; and

[0108] applying a non-excitatory electric field to the portion of the GItract adjacent the tip of the probe, which electric field is operativeto relax the portion of the GI tract.

[0109] Preferably, the method includes inflating the portion of the GItract after applying said field.

[0110] Preferably, the portion of the GI tract is a portion adjacent abile duct.

[0111] There is also provided in accordance with a preferred embodimentof the invention, a method of advancing an elongated probe having a tipand inserted in a portion of the GI tract, comprising:

[0112] applying a first electric field at the tip, which fieldconstricts the portion of GI tract to grasp the probe; and

[0113] applying a second electric field to a second portion of the GItract adjacent a portion of the probe distal from the tip, whichelectric field causes the elongation of the second portion of the GItract.

[0114] Preferably, the method includes applying a third electrical fieldto a third portion of the GI tract, adjacent portions of the probedistal from the tip, which electrical field relaxes the third portion ofthe GI tract so that it does not constrict around the probe.

[0115] Alternatively or additionally, the method includes applying aninhibitory electric field to block the propagation of activation signalsbetween the first portion and other portions of the GI tract.

[0116] There is also provided in accordance with a preferred embodimentof the invention, a method of advancing an elongated probe, comprising:

[0117] providing an elongated probe, having a tip, inside a portion of aGI tract; and

[0118] applying an excitatory electric field to the portion of the GItract, which excitatory electric field causes the bowel to transport theprobe in a desired direction.

[0119] Preferably, the excitatory field is selectively applied either atthe tip or at a different location along the probe, distal from the tip,depending on the desired direction of transport.

[0120] Alternatively or additionally, the method includes applying aninhibitory electric field, to the portion, to block the propagation ofactivation signals between the portion and the rest of the GI tract.

[0121] In a preferred embodiment of the invention, the probe is anendoscope. Alternatively, the probe is a colonoscope.

[0122] There is also provided in accordance with a preferred embodimentof the invention, an elongated probe adapted for advancing in a GItract, comprising:

[0123] an elongated body having a tip;

[0124] a plurality of electrodes disposed at least at the tip; and

[0125] a controller which selectively electrifies the electrodes toproduce non-excitatory electric fields which affect the contraction ofsmooth muscle.

[0126] Preferably the probe includes a second plurality of electrodesdistributed along at least a portion of the body of the probe.

[0127] Alternatively or additionally, the controller electrifies saidfirst plurality of electrodes to cause said portion of GI tract toselectively advance or retreat said probe.

[0128] Alternatively or additionally, the controller electrifies ones ofsaid first and said second pluralities of electrodes to inhibit thepropagation of activation signals from the portion of the GI tractadjacent the tip of the probe to other portions of the GI tract.

[0129] There is also provided in accordance with a preferred embodimentof the invention, a method of controlling a uterus, comprising:

[0130] determining a portion of the uterus suspected of generatingundesirable activation signals; and

[0131] applying a local inhibitory electrical field, to the uterusmuscle, around the suspected portion.

[0132] There is also provided in accordance with a preferred embodimentof the invention, a method of controlling a uterus, comprising:

[0133] determining a portion of the uterus suspected of generatingundesirable activation signals; and

[0134] applying a local desensitizing electrical field to the suspectedportion.

[0135] There is also provided in accordance with a preferred embodimentof the invention, a method of controlling labor, comprising:

[0136] determining a local activation at a plurality of locations of auterus; and

[0137] applying a non-excitatory electric field, to each of theplurality of locations, at a time delay from said local activation time.

[0138] Preferably, the non-excitatory field increases the force ofcontraction at ones of said plurality of locations.

[0139] Alternatively or additionally, said non-excitatory field reducesthe force of contraction at ones of said plurality of locations.

[0140] Alternatively or additionally, the non-excitatory field inhibitsthe conduction of propagating action potentials across the uterus.

[0141] In a preferred embodiment of the invention, the method includesimplanting a plurality of electrodes at the plurality of locations.Preferably, the electrodes comprise encapsulated power sources.Alternatively or additionally, the implanting is performed during acesarean section.

[0142] There is also provided in accordance with a preferred embodimentof the invention, a method of aiding birth, comprising applying anon-excitatory electrical field to a birth canal, which non-excitatoryfield relaxes the birth canal.

[0143] There is also provided in accordance with a preferred embodimentof the invention, a method of preventing premature birth, comprisingapplying a non-excitatory electrical field to a birth canal, whichnon-excitatory field increases the force of contraction in the birthcanal.

[0144] There is also provided in accordance with a preferred embodimentof the invention, a method of treating cramps of the uterus, comprising:

[0145] detecting electrical or mechanical activity in at least onelocation of the uterus; and

[0146] applying a non-excitatory electrical field at the at least onelocation.

[0147] There is also provided in accordance with a preferred embodimentof the invention, a method of treating cramps, comprising:

[0148] providing at least one electrode inside the uterus, which oneelectrode is in contact with at least a portion of the uterus, at atleast one location thereof; and

[0149] applying a non-excitatory electrical field to the portion.

[0150] In a preferred embodiment of the invention, the non-excitatoryfield inhibits the propagation of activation signals at the at least onelocation. Alternatively or additionally, non-excitatory field reducesthe force of contraction at the at least one location.

[0151] There is also provided in accordance with a preferred embodimentof the invention, apparatus for controlling a smooth muscle, comprisinga plurality of individual capsules, each capsule including at least oneelectrode and a power source which electrifies the electrode, whichelectrode applies a local non-excitatory field. Preferably, each of saidcapsules includes a sensor which measures local activity of the smoothmuscle.

[0152] Alternatively or additionally, the capsules are operative tosynchronize the electrification of their electrodes without themeditation of an external controller.

[0153] There is also provided in accordance with a preferred embodimentof the invention, apparatus for treating cramps, comprising:

[0154] a flexible body having an outside portion and adapted to snuglyengage the inside of a uterus;

[0155] a plurality of electrodes disposed on the outside of said body;and

[0156] a controller which electrifies said electrodes to generate anon-excitatory electrical field.

[0157] Preferably, the flexible body is inflatable. Alternatively oradditionally, the apparatus includes a second electrode adapted to beplaced outside the uterus.

[0158] There is also provided in accordance with a preferred embodimentof the invention, a method of controlling a circulatory system,including a heart, comprising:

[0159] providing electrodes adjacent a vein; and

[0160] electrifying the electrodes to constrict the vein, such that thepreload on the heart is increased.

[0161] There is also provided in accordance with a preferred embodimentof the invention, a method of controlling a circulatory system,including a heart, comprising:

[0162] providing electrodes adjacent a vein; and

[0163] electrifying the electrodes to expand the vein, such that thepreload on the heart is reduced.

[0164] There is also provided in accordance with a preferred embodimentof the invention, a method of controlling a circulatory system,including a heart, comprising:

[0165] providing electrodes adjacent an artery; and

[0166] electrifying the electrodes to constrict the artery, such thatthe afterload on the heart is increased.

[0167] There is also provided in accordance with a preferred embodimentof the invention, a method of controlling a circulatory system,including a heart, comprising:

[0168] providing electrodes adjacent an artery; and

[0169] electrifying the electrodes to expand the artery, such that theafterload on the heart is reduced.

[0170] There is also provided in accordance with a preferred embodimentof the invention, a method of controlling vascular spasm, in acirculatory system having a heart, comprising:

[0171] determining a vessel in spasm, which results in an abnormallyconstricted lumen; and

[0172] applying a non-excitatory electric field to the vessel, whichfield causes the lumen to expand.

[0173] It should be appreciated that two or more of the above methods ofcontrolling the circulatory system may also be practiced together.

[0174] In a preferred embodiment of the invention, the method includesapplying a non-excitatory electric field to at least a portion of theheart.

[0175] There is also provided in accordance with a preferred embodimentof the invention, apparatus for controlling a circulatory system havinga heart, comprising:

[0176] a plurality of electrodes disposed about at least one major bloodvessel;

[0177] a blood pressure sensor which measures blood pressure; and

[0178] a controller which electrifies the plurality of electrodesresponsive to the measured blood pressure.

[0179] Preferably, the apparatus includes an external control whichactivates said controller.

[0180] Alternatively or additionally, the apparatus includes an ECGsensor which detects the cardiac rhythm. Alternatively or additionally,the controller relaxes said blood vessel to reduce the blood pressure.Alternatively or additionally, the controller contracts said bloodvessel to increase the blood pressure.

[0181] There is also provided in accordance with a preferred embodimentof the invention, a method of controlling the output of a gland,comprising:

[0182] providing at least one electrode near the gland; and

[0183] applying a non-excitatory electric field to the gland.

[0184] Preferably, the non-excitatory electric field inhibits theactivity of hormone producing cells in the gland. Alternatively oradditionally, the non-excitatory electric field is a substantially DCfield. Preferably, the method includes periodically changing thepolarity of the field. Preferably, one polarity is applied for asignificantly larger portion of the time.

[0185] In a preferred embodiment of the invention, the gland is apancreas. Preferably, the method includes monitoring a level of glucosein the blood, wherein applying said electric field comprises applyingsaid field responsive to said monitored level.

[0186] There is also provided in accordance with a preferred embodimentof the invention, apparatus for controlling the output of a gland,comprising:

[0187] a sensor for measuring a level of a chemical in a blood stream;

[0188] at least one electrode adjacent said gland; and

[0189] a controller which electrifies said electrode with anon-excitatory electric field, responsive to the measured level.

[0190] Preferably, the chemical is glucose. Alternatively oradditionally, the apparatus is completely implantable.

[0191] There is also provided in accordance with a preferred embodimentof the invention, a method of controlling the activation profile of asmooth muscle organ, comprising:

[0192] determining a desired activation profile for the organ; and

[0193] applying at least one non-excitatory field to a portion of theorgan to modify its activation profile.

[0194] Preferably, the activation profile comprises a mechanicalactivation profile.

[0195] In a preferred embodiment of the invention, the method includes:

[0196] measuring a tension in the smooth muscle; and

[0197] modifying the application of the non-excitatory field responsiveto the measured tension.

[0198] Alternatively or additionally, the method includes:

[0199] measuring a pressure in the smooth muscle; and

[0200] modifying the application of the non-excitatory field responsiveto the measured pressure.

[0201] Alternatively or additionally, the method includes applying atleast one excitatory electric field to the smooth muscle.

[0202] Alternatively or additionally, the method includes applying anon-excitatory field comprises applying an inhibitory electric field tothe muscle.

[0203] Alternatively or additionally, applying a non-excitatory fieldcomprises applying an electric field which reduces the force ofcontraction in the muscle.

[0204] Alternatively or additionally, applying a non-excitatory fieldcomprises applying an electric field which increases the force ofcontraction in the muscle.

[0205] Preferably, the organ is a stomach. Alternatively oradditionally, the organ is a small intestine. Alternatively oradditionally, the organ is a large intestine. Alternatively oradditionally, the organ is a uterus.

[0206] There is also provided in accordance with a preferred embodimentof the invention, apparatus for dictating a mechanical activationprofile to a smooth muscle organ, comprising:

[0207] at least three electrodes, adapted to be distributed over theorgan;

[0208] at least one sensor which senses local mechanical activity of theorgan; and

[0209] a controller which electrifies selected ones of said electrodes,responsive to the sensed local mechanical activity, to dictate aparticular activation profile to the organ.

[0210] Preferably, the organ is a uterus and wherein the activationprofile is a pattern of contraction during labor.

[0211] Although many embodiments of the present invention are describedherein mainly as methods, it should be appreciated that the scope of theinvention includes apparatus adapted to perform these methods. Inparticular, the scope of the invention includes programmable electricfield generators which are programmed to supply an electric field inaccordance with a preferred embodiment of the invention. In a preferredembodiment of the invention, programmable variables include, waveforms,amplitudes, frequencies, durations, delays, synchronization and responseto locally measured parameters of muscle activity. It should beappreciated that the behavior of a muscle in one portion thereof can bemodified by applying an electric field to a second portion thereof, forexample, by inhibiting the propagation of an activation signal to theone portion or by changing the layout of forces acting on the oneportion.

BRIEF DESCRIPTION OF THE DRAWINGS

[0212] The present invention will be more clearly understood from thefollowing detailed description of the preferred embodiments of theinvention, together with the accompanying figures, in which:

[0213]FIG. 1 is a schematic illustration of a gastrointestinal (GI)tract;

[0214]FIG. 2 is a schematic illustration of an unfolded GI tract,illustrating various preferred embodiments of the present invention;

[0215]FIG. 3 is a partial cut-through schematic illustration of alaid-open portion of the GI tract, showing the orientation of smoothmuscle fibers of the GI tract;

[0216]FIG. 4 illustrates a method of advancing a colonoscope using localcontrol of the GI tract;

[0217]FIG. 5 is a schematic illustration of a capsule for treatment ofhemorrhoids in accordance with a preferred embodiment of the presentinvention;

[0218]FIG. 6 is a schematic diagram of a uterus, illustrating applyinglocal inhibitory electric fields to small portions of the uterus, inaccordance with a preferred embodiment of the present invention;

[0219]FIG. 7 illustrates an implantable multi-site stimulator/inhibitor,attached to a uterus, in accordance with a preferred embodiment of theinvention;

[0220]FIG. 8 illustrates a balloon-type insert for a uterus, forcontrolling cramps;

[0221]FIG. 9 illustrates a controller which modifies the output of agland, such as the pancreas;

[0222]FIG. 10 illustrates a blood pressure and/or heart load controller,attached to major blood vessels, in accordance with a preferredembodiment of the invention;

[0223]FIG. 11 is a schematic illustration of an experimental setup usedto determine effects of a non-excitatory field on smooth muscle cells;

[0224]FIG. 12 is a graph of experimental results showing an increase inthe force of contraction of a smooth muscle, as a result of theapplication of a non-excitatory electric field, in accordance with apreferred embodiment of the invention;

[0225] FIGS. 13-17 are graphs of experimental results each showing asignificant decrease in the force of contraction of a smooth muscle, asa result of the application of a non-excitatory electric field inaccordance with a preferred embodiment of the invention;

[0226]FIG. 18 is a graph of experimental results showing an increase inthe force of contraction of a smooth muscle of the urine bladder, as aresult of the application of a non-excitatory electric field, inaccordance with a preferred embodiment of the invention; and

[0227]FIG. 19 is a graph of experimental results showing a decrease inthe force of contraction of a smooth muscle of an unpaced uterus, as aresult of the application of a non-excitatory electric field, inaccordance with a preferred embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0228]FIG. 1 is a schematic illustration of a gastrointestinal (GI)tract 22 of a patient 20. In accordance with a preferred embodiment ofthe invention, local control of the force of contraction and/or thesensitivity of portions of the GI tract to excitation is achieved byapplying local, non-excitatory electric fields directly to the portionto be controlled. Although such non-excitatory electric fields do notcreate a propagating action potential in the controlled portion, thefields does modify the response of the portion to an artificial ornaturally occurring activation signal, when it arrives. In particular,the inventors have found that it is possible to increase or to decreasethe force of contraction of a portion of GI tract. In addition, it ispossible to desensitize a muscle segment so that it has a reducedreaction or so it does not react at all to normal amplitudes ofactivation signals. This desensitization, while reversible, may be madeto last a certain period of time after the removal of the controllingelectric field.

[0229] Two particular waveforms of non-excitatory electric fields havebeen found to be beneficial. A first type is a substantially constantfield (whose polarity may be occasionally switched to reduce ionicpolarization effects). This field may be applied without anysynchronization to the controlled muscle. However, the inventors havefound it useful to stop the inhibiting field shortly before theactivation signal is to arrive at the controlled muscle, so as to reducethe amplitude of activation signal required to excite the controlledmuscle. A second type of non-excitatory field is a pulse which isapplied in synchrony with the arrival of an activation signal. The pulseis applied either before, during the arrival of the signal or at a delayafter its arrival (a long enough delay after activation is equivalent toapplying the pulse before activation). The inventors believe that anon-excitatory electric field applied after the activation signal tendsto increase the force of contraction of the controlled muscle, byincreasing a plateau duration of the muscle contraction. It ishypothesized that a non-excitatory field applied at a greater delayafter the arrival of the activation signal extends the refractory period(possibly by hyperpolarizing the muscle cells so that the activationsignal does not cause a depolarization). As a result, at least some ofthe muscle cells do not respond to the activation signal and the forceof contraction of the muscle is reduced. Thus, the stronger thenon-excitatory signal, the more cells will be hyperpolarized and thelower will be the force of contraction. In an extreme case, none of themuscle cells will respond to the activation signal and the propagationthereof will be inhibited. It is also possible that the non-excitatoryfield directly reduces affects the force of contraction achieved by asingle muscle fiber.

[0230] It should be noted that various embodiments of the presentinvention, as described herein, can be used in conjunction with drugtherapies, with a synergistic interaction and/or to allow a reduced doseof drug to produce a desired effect and/or to allow increased dosages ofdrugs to be used, while limiting their adverse side effects usingelectrical control. In addition, such electrical control may bepracticed together with electrical pacing of the GI tract, includingmulti-site pacing. In accordance with a preferred embodiment of thepresent invention, substantially any activation profile of the GI tractmay be achieved by selectively pacing portions of the GI tract andcreating desensitized regions between the paced portions, so that anactivation signal does not propagate from one paced portion to the next.In addition, such electrical control may also be practiced incombination with electrical stimulation of a vagus nerve.

[0231] The term “electric field” has been used to described thenon-excitatory field used to control a muscle. The terms “field” and“current pulse” are used interchangeably herein, since, in the body,both are generated when a voltage potential is created between twoelectrodes. In a preferred embodiment of the invention, the field isapplied by maintaining a constant current between at least twoelectrodes. Alternatively, a voltage potential may be controlled insteadof controlling the current.

[0232] Muscle tissue generally adapts to frequent and/or intenseactivation by increasing its mass. In a preferred embodiment of theinvention, the pacing location is chosen to increase the strength of themuscle at the location. Preferably, the area around the location isdesensitized so that the activation signal does not propagate to therest of the GI tract. Alternatively or additionally, local muscle massis increased by modifying the force of contraction at the location.Generally, a maximum force of contraction is desired, since it willgenerally cause the greatest increase in muscle mass.

[0233]FIG. 2 is a schematic drawing of GI tract 22, unfolded forillustrative purposes, for illustrating various preferred embodiments ofthe present invention. GI tract 22 includes a stomach 24, a duodenum 26,a small intestine 27 and a large intestine 29.

[0234] In accordance with a first preferred embodiment of the invention,a portion of the GI tract is desensitized and/or electrically isolatedfrom activation signals. Isolation from electrical signals may beachieved by desensitizing tissue which surrounds the portion.

[0235] Ulcers cause inflammation of the GI tract tissue, which inflamedtissue may generate spurious activation signals. Alternatively, theinflamed tissue may exhibit a very low threshold of excitability. Boththese abnormalities may cause arrhythmias in stomach 24. In a preferredembodiment of the invention, an ulcer 28 is prevented from generatingabnormal electrical activity in stomach 24 by desensitizing the tissuesurrounding the ulcer. Depending on the exact configuration, ulcer 28itself may be desensitized. Alternatively or additionally, anon-excitatory field will be applied to regions surrounding ulcer 28 tofence it in by non-action potential propagating tissue.

[0236] The term fencing, as used herein, refers to electricallyisolating one segment of muscle from other segments, by inhibitingelectrical activity in the tissue surrounding the one segment. Thus, anactivation signal can neither enter nor leave the one segment.Alternatively to completely enclosing a segment, fences can be used tochannel an activation signal along a desired path by creating fences oneither side of the desired path. It should be noted that in channeling,it my be sufficient to significantly reduce the conduction velocity inthe tissue where the fence is applied, since this will also modify thepropagation vector of the activation front.

[0237] In a preferred embodiment of the invention, the tissuedesensitization is accomplished by a controller 32, comprising anelectrode 30, in contact with the tissue surrounding ulcer 28. Althoughin this embodiment, controller 32 is shown to be external to stomach 24and either inside or outside the body, in an alternative preferredembodiment of the invention, controller 32 is implanted inside thestomach, preferably placed by the aid of an endoscope and/or anelectrical activity mapping probe, and preferably fixed to the wall ofstomach 24, such as by using clips.

[0238] In accordance with another preferred embodiment of the invention,the pacemaker portion of stomach 24, which is usually in the upperportion of stomach 24, is electrically isolated from other portions ofthe stomach. In FIG. 2 this is accomplished by applying a fence 25 in aband around stomach 24. Alternatively or additionally, the rest ofstomach 24 may be desensitized. Alternatively or additionally, thepacemaker region itself may be desensitized to reduce its excitationrate. Desensitizing stomach 24 is useful for treating nausea, pregnancyrelated nausea, reflex vomiting and other stomach conditionscharacterized by undesirable activation of the stomach.

[0239] A particular example of a condition is in the treatment ofobesity, treatable by stomach desensitization, where delaying emptyingof stomach 24 leads to a “full” feeling and reduces the consumption offood by the patient. Desensitization of the stomach is preferablyapplied together with pacing of the stomach to achieve the desiredactivation. Alternatively or additionally, intestines 27 are alsocontrolled in a like manner, especially by blocking electricalactivation signals from stomach 24 from arriving at intestine 27, suchas by applying a fence at duodenum 26 and/or at the antrum. In suchexamples, controller 32 is preferably controllable from outside thebody, such as by using magnetic reed switches or using RF telemetry.Thus, controller 32 may activated and deactivated when the patient needsit. Alternatively or additionally, controller 32 includes sensors whichsense various states of GI tract 22, including, the location of food ina portion thereof and local electrical activity. In such an embodiment,controller 32 can modify the activation profile of GI tract 22,responsive to the existence and position of food matter therein.

[0240] In accordance with another preferred embodiment of the invention,a portion of GI tract 22 is desensitized and/or fenced in to allow it toheal. FIG. 2 shows a sutured region 38, and a controller 40 whichapplies a pair of fences 42 and 44, so that region 38 will beelectrically isolated and so that local muscle activity will not damagethe suture. Region 38 might also comprise an area from which an ulcerhas been recently removed. In a preferred embodiment of the invention,such a controller is incorporated in an anastomosis button, which isused to connect two segments of the intestine. Preferably, such ananastomosis button senses electrical activity at one side thereof andapplied an excitatory signal at an opposite side thereof to assure anatural contraction of the intestines. Alternatively to completelyinhibiting electrical activity at region 38 it may be desirable tointermittently allow local electrical and/or mechanical activity.Alternatively or additionally, the local force of contraction may besubstantially reduced so as to reduce local stretching of the sutures.In a preferred embodiment of the invention, electrodes are implanted atthe treated region during a laproscopic procedure (or an open-abdomenprocedure). An inhibitory electrical field is applied until it is deemedunnecessary by medical opinion.

[0241] In a preferred embodiment of the invention, the electrodes areconnected to an external muscle controller. Once the field is notnecessary, the electrodes may be retracted, for example, using pull-outelectrodes, as known in the art, for example, by twisting the electrodesor by releasing a suture which attaches the electrode to the muscle.

[0242] In a preferred embodiment of the invention, emptying of a stomais inhibited by desensitizing the last few inches of the stoma, untilsuch time as emptying thereof is desired. A controller for a stomapreferably includes electrodes implanted along the last few inches ofthe stoma for applying inhibitory or excitatory pulses. A stomacontroller preferably also includes an external control button whichallows the patient to choose between inhibiting the stoma, to stopexiting of solid wastes and stopping the inhibiting and/or stimulatingthe stoma, to allow travel of solid wastes along the stoma.

[0243] In a preferred embodiment of the invention, an electricalcontroller is used in lieu of a pharmaceutical to relax the bowels. Oneexample which such a used is desirable is in spastic constipation, wherea vicious cycle of tension-pain-constipation can be broken by relaxingthe tension in the large intestines. A relaxing electrical field may beapplied tanscutaneously, by implanted electrodes or may be applied usingan inserted probe.

[0244] In another preferred embodiment of the invention, pains caused byischemia of the intestines are reduced by reducing the contractility ofthe muscle at the diseased area, thereby reducing oxygen consumptionand/or allowing better perfusion. Preferably, such a controller includesa pressure sensor and the controller is adjusted to reduce the force ofcontraction after a preset local force of contraction is reached.

[0245] In another preferred embodiment of the invention, acute diarrheais treated by relaxing small intestine 27 and/or large intestine 29, sothat they do not expel liquids. Such treatment may be advantageouslyapplied using a probe with electrodes mounted thereon. The electrodesare preferably spring electrodes which extend (radially) from the probeto assure good contact with the intestinal wall. This treatment is alsouseful for patients have a chronic irritated bowel, such as patientsusing strong medication and AIDS patients. In patients with a chronicproblem, electrodes are preferably implanted on the outside of portionsof the GI tract.

[0246] Another aspect of the present invention relates to increasing thecontractility of at least a portion of GI tract 22, typically, tocompensate for a medical conditions where the contractility of at leasta portion of GI tract 22 is reduced to below normal levels. Suchconditions are typical in older patients. Subnormal contraction forcesare also found in patients in whom a portion of the bowel is denervated,in particular, in patients having Aclazia (acquired or chronic) and inother disorders such as diffuse systemic sclerosis, diabetic enteropathyand primary visceral myopathies. In such conditions, the non-excitatoryelectric field is preferably applied using wire electrodes which areeither attached to the inside of GI tract 22, implanted in the muscle ofGI tract 22 itself and/or using electrodes which are implanted on theoutside surface of GI tract 22. Preferably, such electrodes areimplanted by advancing a surgical probe along the outside of GI tract 22and attaching electrodes at locations along the outside of the tract.Alternatively, a plurality of encapsulated controllers may be implantedat a plurality of points along GI tract 22. Each encapsulated controllerincludes a power source, electrodes and a controller which can beactivated by external command to apply a non-excitatory field.Alternatively, each such encapsulated controller comprises an inductioncoil which converts RF radiation, which is transmitted to the coil froman external source, to a non-excitatory electric field.

[0247] Another aspect of the present invention relates to simultaneouslyapplying several different types of control so as to achieve moreprecise control of the activation profile of GI tract 22. In onepreferred embodiment of the invention, the motility of small intestine27 and/or large intestine 29 is increased by inhibiting a returningwave. In a normally activated intestine, there is a forward wave whichadvances food matter in the intestine and also a returning wave, whichcauses the food to retreat along the intestine and assists in churningthe food. In this preferred embodiment of the invention, the forwardwave is not inhibited and the returning wave is inhibited so as to allowgreater motility, Preferably, the returning wave is inhibited at itsorigin, the end of the intestine, by applying a fence at the location.FIG. 2 shows a controller 46 which applied a fence 48 at the end ofsmall intestine 27. Preferably, controller 46 uses a sensor 52 and/or asensor 50 to detect the forward wave and/or the returning wave, eitherby their electrical activity or by their mechanical action. In apreferred embodiment of the invention, fence 48 is synchronized to theforward wave and applied only enough time to block the returning wave.Controller 46 is preferably inserted using an endoscope, preferably,from inside the small intestine.

[0248] In accordance with another preferred embodiment of the invention,electrical control is used to advance a stuck bolus 56. To advance bolus56, electrical control is applied to an area 60, forward of bolus 56, torelax it. An area 58, behind and around bolus 56 is preferablycontrolled to increase its contractility. A controller 54 may bepermanently implanted at location 58, if, due to damage to nerve and/ormuscle, boluses are expected to be stuck at this location. In apreferred embodiment of the invention, a significant portion of GI tract22 is wired. A plurality of sensors are placed along the portion todetect a bolus in the portion. Thereafter, the above described methodfor advancing the bolus is applied at the detected location. Theplurality of sensors may be impedance sensors, which preferably use thesame electrodes as the field applying electrodes.

[0249]FIG. 3 is a partial cut-through schematic illustration of alaid-open portion 72 of GI tract 22, showing the orientation of smoothmuscle fibers of the GI tract. GI tract 22 is typically composed ofthree muscle layers, a thin, electrically conducting layer (not shown),a inner layer 72 of fibers aligned generally along the length of GItract 22 and an outer layer 74 of fibers aligned generally perpendicularto the fibers in layer 72. Layer 72 controls local changes in length ofGI tract 22, while layer 74 controls local changes in diameter of GItract 22.

[0250] In a preferred embodiment of the invention, a non-excitatoryelectrical field is selectively applied either to layer 72 or to layer74, to either increase or decrease the local force of contraction. Thisselectivity may be achieved by aligning the direction of the electricfield either in parallel to fibers in layer 72 or in parallel to fibersin layer 74. It should be noted that this type of selectivity is notpossible when using an excitatory electric field, since such a fieldexcites both layers 72 and 74.

[0251] In a preferred embodiment of the invention, a net electrode 76,having a plurality of individual electrodes 78, is used to affect thisselectivity. If the net is placed so that its main axes are parallel tothe fiber directions, an electrical field, having a direction parallelto one of the layers may be generated by choosing selected ones ofelectrodes 78. Ones of electrodes 78 can also be selected to apply afield which is diagonal to fibers in both layers. Alternatively oradditionally, electrodes 78 are alternatively electrified, so thatelectric fields in both directions are alternatively applied. Inparticular, an inhibitory field may be applied in one direction while acontractility increasing field may be applied in the perpendiculardirection. As can be appreciated, electrodes 78 may also be used tosupply a pacing signal. In a preferred embodiment of the invention,electrodes 78 are also used to sense local electrical activity so as tobetter time the non-excitatory field.

[0252] Another type of electrode which is preferred for use incontrolling smooth muscle, is an elongated electrode which is useful forapplying an inhibiting electrical field, to create a fence. Thepropagation of an activation signal is most advantageously controlled(increased or decreased) by applying an electric field which is parallelto the fibers in the innermost layer of muscle, since that muscle layerconducts the activation signal. The propagation of the activation signalmay be increased by applying a contractility enhancing electric field tothe inner layer. Another method of selectively applying an electricfield to only one layer is to insert the electrodes into the muscle,between the layers, so that substantially only one layer is inside thefield.

[0253] Various apparatus for and methodologies for applying anon-excitatory electric field to cardiac muscle are described in six PCTapplications, filed by applicant New Technologies (SA-YSY) Ltd. et al.,in the Israel receiving office: PCT application PCT/IL97/00012,“Electrical Muscle Controller”, filed Jan. 8, 1997, and five PCTapplications filed on Jul. 9, 1997: PCT/IL97/00231, “Apparatus andMethods for Controlling the Contractility of Muscles”, PCT/IL97/00232,“Drug-Device Combination for Controlling the Contractility of Muscles”,PCT/IL97/00233, “Fencing of Cardiac Muscle”, PCT/IL97/00235 “CardiacOutput Controller” and PCT/IL97/00236, “Cardiac Output EnhancedPacemaker”, the disclosures of which are incorporated herein byreference. In particular, these PCT applications describe variouswaveforms which may be used for applying non-excitatory electric fields,including, DC fields, AC fields, unipolar and bipolar fields andcombinations of such fields. Further, PCT/IL97/00012 also describes thepossibility of using light radiation and RF radiation to affect calciumtransfer in cardiac muscle cells and thereby affect their force ofcontraction. These apparatus may be adapted, in accordance withpreferred embodiments of the present invention to supply non-excitatoryelectric fields to smooth muscles.

[0254] When adapting the apparatus described herein to a particularphysiology, it is expected that the amplitudes, delays and frequenciesof the non-excitatory may need to be adapted. In a preferred embodimentof the invention, the apparatus is programmable by RF radiation. Thus,it can be implanted and different sets of pulse parameters may be testedto determine an optimal set. Additionally, the parameters may need to beadjusted after a time, due to adaptation of the controlled muscle,changes in impedance of the electrodes or to change the function of thecontroller.

[0255] As will be appreciated, some patients will require only a shortcourse of treatment, while other patients will require a longer course,in some cases, a permanent treatment will be required. In a preferredembodiment of the invention, apparatus, as described herein is adaptedto be implanted in the body, Alternatively, such apparatus is adapted tobe inserted in the body, for a shorter period of time, such as under amonth. This adaptation may provide for using different materials for theelectrodes and for a different tradeoff between battery life and degreeof control. Alternatively, such apparatus is adapted to be external tothe body, either carried by the patient or free-standing. Preferably, atleast the electrodes are implanted in the body or inserted in a bodylumen.

[0256] It should also be noted that the activity of smooth muscles isalso modified by their tension. In a preferred embodiment of theinvention, a controller for smooth muscle includes sensors which measurethe tension in the muscle and modifies the applied field responsive tothe measured tension. Preferably, the tension is measured on the outsideof the lumen of the smooth muscle. Alternatively or additionally, thetension is measured inside the lumen formed by the smooth muscle.Alternatively or additionally, the tension is measured inside the smoothmuscle.

[0257] In a preferred embodiment of the invention, the orientation andpolarity of the electric field relative to the muscle fibers are alsovaried to determine an optimal orientation and/or polarity which effectthe desired control on the muscle. It should be noted that the twoperpendicular muscle layers have different characteristics, such asresting tension, and, probably, a different response to thenon-excitatory field. In a preferred embodiment of the invention,various orientations of the electric field to the muscle fibers, such as0°, 5°, 10°, 30° and 45°, are tested without moving the electrodes. Thisis preferably achieved using a net-type electrode, where each junctionof the net may be individually electrified. Thus substantially anyeffective field direction and polarity may be tested without moving theelectrodes. Such a net electrode can also be used as a sensor net tomore precisely determine the propagation direction of an activationfront, as this propagation direction will generally be perpendicular toiso-chronal lines which mark equal activation times. In addition,changes in the activation profile, such as the effect of the controllingfields and/or arrhythmias can be detected from changes in the electricalsignals sensed at the plurality of junctions of the net. In addition,mechanical activity may be localized by impedance measurement betweenindividual ones of the junctions, either neighboring junctions, in whichcase characteristics of the muscle are measured or junctions which areon opposite sides of the smooth muscle, in which case occupancy of theGI tract may be determined.

[0258] It should be noted that the frequency of contraction of smoothmuscle is usually much lower than cardiac muscle, enabling the use ofsimpler electronics and slower-responding power sources, for controllingsmooth muscle. Furthermore, the propagation time along smooth muscle isusually much slower than for cardiac muscle. As a result, severalseconds may pass between the activation time at one location and theactivation time at a second location. Thus, to ensure a proper delaybetween local activation and local application of a non-excitatoryfield, local determination of activation time is especially preferredfor smooth muscle control. Such local determination is preferablyperformed by local sensing, however, in other preferred embodiment ofthe invention, the local activation time is calculated using anestimated propagation velocity.

[0259]FIG. 4 illustrates a method of advancing a colonoscope 90 usinglocal control of a portion 92 of GI tract 22. As minimally invasiveprocedures gain acceptance, periodic examination of the large intestine,using a colonoscope and of the small intestine, using an endoscope arebecoming more common. In colon examination, the colonoscope is insertedinto the anus and advanced along the colon. Periodically, the advance isstopped and the colon, surrounding the tip of the colonoscope, isinflated using air, so as to aid the advance of the colonoscope and toaid the examination of the colon wall. Drugs which relax the colon areusually administered to the patient prior to the examination.

[0260] In accordance with a preferred embodiment of the invention, acolonoscope 90 has a plurality of electrodes 94 at least at its tip. Ina preferred embodiment of the invention, these electrodes are used toapply a relaxing electric field to the colon and thus, reduce the airpressure required to inflate it. In addition, such relaxing reduces theforce required to advance the colonoscope, thereby reducing the dangerof perforation. In a preferred embodiment of the invention, theelectrodes are extendible from the tip of colonoscope 90 so that theycan engage colon portion 92 even when it is inflated. Preferably, theelectrodes can be temporarily hooked onto colon portion 92.

[0261] In accordance with another preferred embodiment of the invention,electrodes 94 are electrified to as to cause colon portion 92 itself toadvance or to aid in the advance, of colonoscope 90. This advance may beachieved in one of two ways, either by blocking the forward wave andallowing the returning wave to advance colonoscope 90 or by selectivelyexciting muscles fibers in layers 72 and 74 (FIG. 3) so as to advancethe colonoscope. One regimen of selective excitation includes:controlling layer 74 to more firmly grasp colonoscope 90 at its tip andexciting layer 72 to advance colonoscope 92. The order of excitation andthe point from which the colon is excited, will, to a great measure,determine the direction of transport of colonoscope 92. Preferably,additional electrodes along colonoscope 90 (not shown) are used eitherto perform the same advancing action or to relax layer 74 along thelength of colonoscope 92, to aid its advance. Selective excitation of aparticular orientation of muscle fibers may be achieved by firstinhibiting the other orientation of muscle fibers and then applying anexcitatory stimulus. Retracting the colonoscope may be assisted bypacing colon potion 92 at the tip of colonoscope 90, so as to use thenatural rhythm of colon portion 92 to retract colonoscope 90.

[0262] As can be appreciated, what has been described for a colonoscopeapplies equally to an endoscope, especially for retracting it. In apreferred embodiment of the invention, colonoscope 90 includeselectrodes which apply a fencing field which blocks any localexcitations from propagating to the rest of GI tract 22.

[0263] In accordance with another preferred embodiment of the invention,an endoscope which is used for entry into the bile duct, includeselectrodes at its tip to apply a relaxing electric field, so as toenlarge the sphincter from the bile duct into the intestines.Preferably, such enlargement, when applied by a device which does notobstruct the bile duct, is used in conjunction with treatments fordestroying gall bladder stones, to aid the exit of broken fragments ofstone into the intestines. Alternatively, such a device is used toexcite and/or increase the contractility of the bile duct to aid in thetransport of such stones and/or to aid in its normal functioning. Anon-obstructing device may be implanted externally to the gall bladderduct, such as inside small intestine 27 and only the leads for theelectrodes need be in the duct. Alternatively, also the leads areimplanted external to the duct.

[0264]FIG. 5 is a schematic illustration of a capsule 102 for treatmentof a hemorrhoid 100 in accordance with a preferred embodiment of thepresent invention. It has recently been determined that a major cause ofhemorrhoids and a major factor in the non-healing of hemorrhoids andanal fissures is increased tension in the lower colon. The increasedtension reduces the flow of blood, delaying healing and, at the sametime, causing pain. It should be noted that tension in the lower part ofthe colon blocks blood from the rectal area, i.e., at some distancethereof. Topically applied Nitroglycerin (both at the hemorrhoids andinside the colon) has been suggested for reducing the tension in thelower colon. However, this drug has several side effects, such asdizziness. In accordance with a preferred embodiment of the invention,capsule 102 is inserted into the lower colon, where it applies relaxingelectric fields, which either completely inhibit local contraction or atleast, reduce it. Capsule 102 preferably includes a plurality ofelectrodes 104, a power supply 106 for electrifying the electrodes and,preferably, an attachment 110 for easy removal of capsule 102.Preferably, capsule 102 senses, using a pressure transducer (not shown)abnormal pressures in the colon and applies a relaxing electrical fieldonly at those times or after such abnormal pressure has continued for asignificant period of time. Alternatively or additionally, a tensionsensor and/or an electrical activity sensor are used to sense the localactivity of the colon.

[0265] In a preferred embodiment of the invention, suitable for femalepatients, capsule 102 is adapted to be inserted into a vagina and applyan electric field which affects the lower colon. Preferably, electrodes104 are arranged so that the field is applied asymmetrically and mostlyin the direction of the colon, since it is generally undesirable toeffect a relaxing field on the muscles of the bladder or on the rectalsphincter. Thus, electrodes 104 are preferably arranged only on one sideof capsule 102. Capsule 102 preferably includes a marking so that thepatient will insert it in the proper orientation. Alternatively to usinga capsule, a controller 108 may be implanted outside the colon.

[0266]FIG. 6 is a schematic diagram of a uterus 120, illustratingapplying local inhibitory electric fields to small portions of thereof.Undesirable electrical activity in the uterus may induce premature laborin women. It is hypothesized that such undesirable electrical activitymay, in many cases be cause by small regions of tissue, for example,near fibroids or myomas, where the stretching of the uterus may bemaximal, or at inflamed locations. Unlike the heart, it may not bedesirable to ablate portions of the uterus, as this may reduce thefertility and/or may irreversibly damage the uterus. In a preferredembodiment of the invention, electrical excitation from a fibroid 122 isblocked from propagating by fencing the fibroid or by desensitizingfibroid 122 and tissue surrounding it. FIG. 6 shows a controller 124which administers such non-excitatory electrical fields using aplurality of electrodes 126. Preferably controller 124 is external touterus 120, but it is preferably implanted inside the body. However, inother embodiments of the invention, only electrodes 126 of controller124 are inserted in the body, for example, using a laproscopicprocedure. Electrodes which need to be inserted into the back of theuterus may be inserted through the intestines.

[0267] Areas of the uterus which might cause such premature electricalactivity may include, inflamed tissue, scar tissue, fibroids andmalformed portions of the uterus. These types of tissue may be detectedeither by visual inspection (using a hysteroscope) or, preferably, usingan electrical mapping probe, as known in the art of electrophysiology.Such mapping may also be performed during pregnancy, in which case theelectrodes may be implanted from inside the uterus, during, or shortlyafter the mapping procedure. The controller will then preferably beexternal to the body, or possibly, in the vagina.

[0268] It has been suggested that there is a small region of the uterus,shown in FIG. 6 as a region 128, which generates a pacing signal for theentire uterus, at least during labor. In a preferred embodiment of theinvention, labor is delayed by selectively inhibiting this area or byfencing it in, using non-excitatory electrical fields.

[0269] One, aspect of the present invention relates to providing a moreexact control over the process of labor than is possible using drugs.Several situations, where the response time of drugs is not sufficient,the side effects too great or proper dosage is difficult to establish,include:

[0270] (a) stopping premature labor;

[0271] (b) stopping a labor where a cesarean section is indicated;

[0272] (c) situations where fine control of the force of contraction ofthe uterus is required;

[0273] (d) assisting a labor which is not advancing properly; and

[0274] (e) stopping labor from ever starting, where it iscontra-indicated.

[0275] (f) dictating a preferred contraction profile during labor.

[0276]FIG. 7 illustrates a implantable multi-site stimulator/inhibitor130, attached to uterus 120, in accordance with a referred embodiment ofthe invention. Controller 130 includes a plurality of electrodes 132,preferably arranged to cover substantially all of uterus 120. Theseelectrodes may be attached to the outside of uterus 120, for exampleduring a laproscopic procedure. Alternatively electrodes 132 areattached to the inside of uterus 120, such as by an hysteroscopicprocedure. Alternatively, these electrodes may be external to the body,such as on the skin, and possible, inserted in the intestines adjacentthe uterus. In a preferred embodiment of the invention, electrodes 132are implanted prior to the pregnancy, such as during a previous cesareansection and/or using a laproscopic procedure. Alternatively oradditionally, electrodes to control smooth muscle are implanted in theblood vessels which adjacent the smooth muscle, such as the vesselswhich supply the smooth muscle. Preferably, the electrification ofindividual ones of electrodes 132 is timed to local electrical activity.Electrodes 132 can also be used to provide a stimulating signal, whichwill both induce and sustain labor.

[0277] In accordance with another preferred embodiment of the invention,multi-site pacing, is used to dictate a preferred activation(contraction) to the uterus. Preferably, multi-site pacing iscomplemented by local control of force of contraction (usuallyincrease). Alternatively or additionally, fences are applied to theuterus, to channels the activation signals in a desired manner. Itshould be noted that fencing may be applied by itself, in combinationwith a single pacing location of in combination with multiple activationlocations, in various preferred embodiments of the invention.

[0278] In accordance with a preferred embodiment of the invention, laboris advanced and/or assisted by increasing the force of contraction. Theincrease in the force of contraction causes a positive feedback effectwhich further increases the force of contraction. An increase in theforce of contraction is also useful for assisting artificial abortions.In other situations, the force of contraction may need to be reduced orlabor may have to be stopped completely, such as in cases of fetaldistress or where there is danger of a rupture of the uterus, in whichcases a cesarean section is to be performed. In cases of malformed orheavily scarred uteruses and in patients having a previous history ofpremature labor, controller 130 is preferably used to stop labor fromever occurring. Preferably, electrodes 132 are electrified to produce aninhibiting electrical field. Preferably, they are electrified only whencontroller 130 detects local electrical activity. Alternatively oradditionally electrodes 132 are electrified responsive to the frequencyof contraction of uterus 120.

[0279] In accordance with another preferred embodiment of the invention,a birth canal 134 and/or a cervix of uterus 120 is relaxed using alocally applied electric field, to aid in exiting of a babytherethrough. Alternatively, the force of contraction of the birth canalis increased prior to labor, to avoid a miscarriage. Alternatively oradditionally, the muscles of the birth canal are also stimulated usingexcitatory signals to cause their contraction and avoid a miscarriage.

[0280] It should be appreciated that uterus 120 undergoes verysignificant changes in size over the course of a pregnancy. Thus, theleads of electrodes 132 are preferably made very flexible and elastic.In one preferred embodiment of the present invention, the leads areformed of a coiled wire, so that if the lead is stretched, the coiltightens, rather than break the wire. Preferably, the coil is woundabout a flexible core. Preferably, the leads of electrodes 132 includeweakened points, such that if strain of above a predetermined value isapplied to the lead it will break at one of the preselected points,rather than damage tissue structures adjacent the lead.

[0281] In a preferred embodiment of the invention, each of electrodes132 comprises an encapsulated power supply and controller 130coordinates the individual electrodes using wireless communication.Thus, electrodes 132 do not need to be interconnected by wires.Alternatively, electrodes 132 are coordinate their electrification usingtechniques well known in the art of distributed computing and without acentral controller. Alternatively to synchronizing their activity, eachof electrodes 132 operates responsive to local activity.

[0282]FIG. 8 illustrates a balloon-type insert 140 for uterus 120, forcontrolling cramps. Insert 140 comprises a plurality of electrodes 142,disposed on the outside of the device, which electrodes are electrifiedby a power source 144. Insert 140 is preferably inflatable to assurebetter contact with the inner wall of uterus 120. In a preferred mode ofoperation, various ones of electrodes 142 function as electricalactivity sensors. Once such electrical activity is sensed, an inhibitingfield is applied at those locations to prevent the future occurrence ofelectrical activation and/or to prevent its propagation. Alternatively,such a device continuously applies an inhibitory electrical field. In apreferred embodiment of the invention, the inhibitory electrical fieldis applied between electrodes 142 and an external electrode which isplaced on the abdomen and/or on the back. Although point electrodes areshown in the figure, it should be appreciated that other forms ofelectrodes, such as elongated electrodes may also be used. Preferably,the device is removed from the body when cramps are not expected.

[0283]FIG. 9 shows a controller 150 which modifies the output of agland, such as a pancreas 152. In some glands, such as pancreas 152,execration of hormones into a blood vessel 154 is meditated byelectrical excitation of the hormone producing cells (beta islet cellsin the pancreas). The electrical excitation, as in many smooth muscles,is initiated by chemical signals. In accordance with a preferredembodiment of the invention, the hormone execrating cells aredesensitized so that they do not respond to these chemical signals, or,if some of the cells do respond, these cells cannot generate apropagating activation signal, since the surrounding cells areelectrically deactivated. Thus, the amount of execrated hormone isreduced. This method is especially useful in diseases, such as tumors,where a gland over produces its hormone.

[0284] Controller 150 preferably includes an electrode 158 and,preferably, a second electrode 156 so as to create an electric fieldwhich inhibits or reduces the electrical activity of the hormoneproducing cells. The casing of controller 150 may be used as the secondelectrode, in this and in other of the above described preferredembodiments. As can be appreciated, the levels of hormone in the bloodand the electrical activity of the hormone producing cells is ratherdifficult to detect using current technology. Thus, in a preferredembodiment of the invention, a substantially constant inhibitoryelectrical field is applied. Preferably, the polarity of the field ischanged periodically, so as to prevent ionic-meditated damage and theionization of electrodes 156 and 158. Alternatively, controller 150 maymeasure local electrical activity, hormone levels or it may measure abodily indicator, such as glucose level, which is correlated with thehormone level and apply a voltage to electrodes 156 and 158, asindicated.

[0285] Another aspect of the present invention relates to controllingblood pressure and/or other circulatory parameters such as the load on aheart. Preferably, the control is exerted in conjunction with the use ofa cardiac controller, such as described in the above referenced PCTapplications. FIG. 10 illustrates a blood pressure and/or heart loadcontroller 160, attached to major blood vessels, in accordance with apreferred embodiment of the invention. A heart 162 receives blood froman abdominal vena cava 168 and pumps it to an aorta 164 and from thereto an abdominal aorta 166. In the event of a spasm in aorta 164, itgreatly constricts, increasing the afterload on the heart. In many casesthis types of spasm will cause dizziness. In patients having constrictedcoronary arteries, the increased cardiac demand may also cause a painfulepisode of angina pectoris.

[0286] In accordance with a preferred embodiment of the invention, theafterload of heart 162 is momentarily reduced by relaxing largearteries. Alternatively or additionally, the preload of heart 162 ismomentarily reduced by relaxing large veins. Reducing either the preloadand/or the afterload, reduces the work demanded from heart 162 and will,in many cases, stop the pain of angina pectoris. Alternatively oradditionally, the walls of the large blood vessels are relaxed in orderto lower the blood pressure, during an acute episode of high bloodpressure. Alternatively, the blood vessels may be constricted, such asduring an acute episode of low blood pressure. Reducing the load onheart 162 is especially beneficial if practiced while extending thediastole of the left ventricle of heart 162, such as by extending therefractory periods of muscle cells therein, for example, as described inthe above mentioned PCT applications.

[0287] The choice of the particular blood vessel to relax depends, interalia, on the type of load which is desirable to reduce, on whether thehypertension is pulmonary or systemic and, in case of a spasm, if thevessel having a spasm has implanted electrodes.

[0288] In a preferred embodiment of the invention, the vessel in spasmis detected using by measuring changes in the impedance between theelectrodes surrounding the blood vessel. Alternatively, rather thandetermining which vessel is in spasm, all wired blood vessels arerelaxed.

[0289] In a preferred embodiment of the invention, controller 160includes a pair of electrodes 170 and 172 for controlling abdominal venacava 168. Alternatively or additionally, controller 160 includes a pairof electrodes 174 and 176 for controlling the abdominal aorta.Alternatively or additionally, controller 160 includes a pair ofelectrode 178 and 180 for controlling the aorta, preferably, at or aboutthe aortic arch. In a preferred embodiment of the invention, theelectrodes are net-type electrodes, since the muscle fibers in bloodvessels are mostly oriented perpendicular to the direction of flow ofblood and a field perpendicular to the blood flow direction isdesirable. Alternatively, the electrodes are elongated electrodes,arranged parallel to the blood flow, to apply a field perpendicular tothe blood flow, between pairs of electrodes. Preferably, controller 160is externally controllable, so that a patient can activate it when hefeels pain and/or dizziness. Alternatively or additionally, controller160 includes a blood pressure sensor (not shown), for automated closedloop blood pressure control. Alternatively or additionally, controller160 includes an ECG sensor or a blood flow sensor, so that theapplication of the fields to the vascular system may be synchronized tothe cardiac rhythm. Preferably, controller 160 includes a fail-safecutoff which prevents the patient from reducing or increasing the bloodpressure beyond acceptable limits.

[0290] FIGS. 11-16 describe experiments which show that the force ofcontraction of a smooth muscle can be increased or decreased byapplication of non-excitatory electric fields directly to the muscle.

[0291] Male, New Zealand White rabbits (1-2Kg body weight) weredissected and various portions of their GI tract were removed and usedfor the following experiments. The animals were anesthetized usingpentobarbitone (Ceva, France), 60 mg/Kg body weight, by IV. Theabdominal wall was opened to expose the abdominal viscera. Requiredportions of the GI tract were removed and placed in a cold (4° C.)oxygenated (95/5 O₂/CO₂) Krebs-Heseleit solution, containing (in mM):KCl 4.5, NaCl 118, NaHCO₃ 24, MgSO₄ 1.19. KH₂PO₄ 1.18, Glucose 11 andCaCl₂ 2.52). The removed portions were then further dissected in adissection chamber (Hugo Sachs Electronik (HSE), Germany) to produce asingle strip of GI muscle which was then placed in an organ bath. Theorgan bath is a type 813 (I-18E) by HSE and it includes a temperaturecontroller type 319 and a force transducer type F30 with a 660 typeamplifier. The elapsed time for the removal procedure is about 3-5minutes.

[0292]FIG. 11 is a schematic illustration of an experimental setup usedto determine the effects of a non-excitatory field on smooth musclecells. A GI muscle portion 200 is fixed in an organ bath chamber, oneend is fixed to the chamber using a plastic clip, while the other end ishooked to a pressure transducer 202. The length of the GI muscle isadjusted to allow maximal isometric force. The organ bath is temperaturecontrolled and the GI muscle is continuously perfused (7-12 ml/min) withthe above described oxygenated solution, maintained at about 36.1° C.The muscle was allowed to remain in the organ bath for a 30 minutesequilibrium period prior to experimentation.

[0293] The organ bath includes two Ag—AgCl electrodes 206 which wereused to apply a pacing pulse, where required by the experimentalprotocol. These electrodes were chlorodized before each experiment. Thepacing stimuli was provided by a constant current source. The pacingwaveform was a square wave pulse. A non-excitatory electric field wasapplied using carbon electrodes 208 (shaped from carbon rods provided byGoodfellow, UK) which were placed about 2-3 millimeters apart. Theelectrodes were electrified by a constant current source 210. The twoconstant current sources were home made current sources whose currentlevel was modified by computer control. The output of these currentsources was continuously monitored to verify that a constant current wasproduced. The entire experiment was controlled by a computer 212 and thedata was acquired using dedicated data acquisition circuits, such as aPCI-MIO-16XE50 or an AT-MIO-16E-2 (National Instrument, USA). The organbath was placed on an anti-vibration table (TMC, USA). Both the pacingcurrent and the non-excitatory current were constant current pulses. Theamplitude of the pacing is different between the following experiments,in the main pat, to counteract polarization of the electrodes. The delayof the non-excitatory field (NT current) is from the start of the pacingsignal.

[0294] FIGS. 12-17 show experimental results using a section of GI tractfrom the Jejunum. The fields were applied and the transducer measuredforce were approximately along the direction of the GI tract. Asdescribed above, variations in the orientation can change the effect ofthe non-excitatory pulse. The polarity of the field was sometimesselected to cause a force increasing effect and sometimes to produce aforce decreasing effect.

[0295]FIG. 12 is a graph of experimental results showing an increase inthe force of contraction of a smooth muscle, as a result of theapplication of a non-excitatory electric field in accordance with apreferred embodiment of the invention. The non-excitatory field is shownas a full bar marked “NT.”

[0296] In this experiment, the pacing was 0.15 Hz, 30 ms duration and 3mA current. The non-excitatory field was a 200 ms current pulse at 10 mAapplied at a delay of 50 ms after the pacing. As seen in FIG. 12, anincrease of about 300% in the force of contraction was achieved.

[0297] FIGS. 13-16 are graph of experimental results showing asignificant decrease in the force of contraction of a smooth muscle, asa result of the application of a non-excitatory electric field inaccordance with a preferred embodiment of the invention.

[0298] In FIG. 13, a 70% reduction in force of contraction was achieved.The pacing was the same as in FIG. 12, while the non-excitatory pulsewas applied for 100 ms, at a 100 ms delay after the pacing and at 10 mA.It should be noted that the effect of the non-excitatory field lastedfor a while after the removal thereof. In addition, the non-excitatoryfield also reduced the base tone of the muscle, i.e., it relaxed it.

[0299] In FIG. 14, a substantial reduction in force of contraction wasachieved. The pacing was faster than in FIGS. 12 and 13: 0.25 Hz, 30 msduration and 10 mA amplitude. The non-excitatory pulse was applied for50 ms, at a 50 ms delay after the pacing and at a 10 mA amplitude. Inthis experiment too, a reduction in muscle tone is observed.

[0300] In FIG. 15, a substantial reduction in force of contraction wasachieved. The pacing was different from that of FIG. 14: 0.25 Hz, 30 msduration and 3 mA amplitude. The non-excitatory pulse was applied for 60ms, at a 200 ms delay after the pacing and at 10 mA. In this experimenttoo, a reduction in muscle tone is observed.

[0301] In FIG. 16, a substantial reduction in force of contraction wasachieved. The pacing was similar to that of FIGS. 12 and 13: 0.15 Hz, 30ms duration and 3 mA amplitude. The non-excitatory pulse was applied for100 ms, at a 50 ms delay after the pacing and at 10 mA. In thisexperiment too, a reduction in muscle tone is observed.

[0302] In FIG. 17, a substantial reduction in force of contraction wasachieved using a substantially constant non-excitatory field. The pacingwas 0.25 Hz, 2 ms duration and 5 mA amplitude. The non-excitatory pulsewas applied for 3990 ms, at a 5 ms delay after the pacing and at anamplitude of 15 mA. A nearly complete blockage of contraction isobserved of In this experiment too, a reduction in muscle tone isobserved.

[0303]FIG. 18 is a graph of experimental results showing an increase inthe force of contraction of a smooth muscle of a urine bladder, as aresult of the application of a non-excitatory electric field, inaccordance with a preferred embodiment of the invention. The bladdersegment was prepared as described above. It was paced at 0.2 Hz, 30 msduration and 6 mA amplitude. The non-excitatory field was a 60 msduration pulse applied at a 30 ms delay after pacing and having anamplitude of 10 mA. It should be noted that the resting tension of thebladder segment also increased as a result of applying thenon-excitatory field.

[0304]FIG. 19 is a graph of experimental results showing an increase inthe force of contraction of a smooth muscle of a rabbit uterus, as aresult of the application of a non-excitatory electric field, inaccordance with a preferred embodiment of the invention. The uterussegment was prepared as described above. The muscle segment was notartificially paced, it was self paced. The non-excitatory field was apulse of 20 ms duration, 10 mA amplitude and applied at 0.2 Hz. Itshould be noted that not only was the force of contraction significantlyreduced, after about 30 seconds of application of the non-excitatoryfield, the contraction of the tissue was apparently completelyinhibited. The effects of the field also lasted for a short time afterthe removal thereof.

[0305] It will be appreciated by a person skilled in the art, thatalthough the present invention has been described with reference to thepreferred embodiments, the scope of the invention is not limited by whathas thus far been described. In particular adaptation of the abovedescribed durations, amplitudes and delays of non-excitatory signals toparticular patients is considered to be within the ability of a man ofthe art and also within the scope of the present invention. Thus, thescope of the present invention is limited only by the claims whichfollow.

1. Apparatus for controlling at least the local activity of a portion ofan in vivo gland, comprising: a plurality of electrodes, adapted to bein contact with a portion of gland to be controlled; and a controllerwhich electrifies said electrodes with an electrical field which doesnot generate a propagating action potential in the gland, whichelectrical field modifies the reaction of the gland to an activationsignal.
 2. Apparatus according to claim 1, further comprising anelectrical activity sensor which detects electrical activity at theportion and wherein the controller electrifies the electrodes responsiveto signals from said sensor.
 3. A method for controlling at least thelocal activity of a portion of an in vivo gland using the apparatus ofclaim 2, wherein applying an electric field comprises applying theelectric field at a delay after a local activation time.
 4. Apparatusaccording to claim 2, wherein the electrification at each of theelectrodes is responsive to its local electrical activity.
 5. Apparatusaccording to claim 2, wherein the electrical activity sensor senseselectrical activity through ones of the plurality of electrodes. 6.Apparatus according to claim 1, further comprising an impedance sensor,which senses at least one impedance between selected ones of theplurality of electrodes.
 7. Apparatus according to claim 2, wherein thecontroller applies an inhibitory electric field to the Gland, when theactivity is above a certain threshold.
 8. Apparatus according to claim1, wherein the non-excitatory field inhibits hormonal secretion at theportion.
 9. Apparatus according to claim 1, wherein the non-excitatoryfield reduces the hormonal secretion at the portion.
 10. Apparatusaccording to claim 1, wherein the non-excitatory field increases thehormonal secretion at the portion.
 11. Apparatus according to claim 1,wherein the controller additionally electrifies at least one of theelectrodes with an excitatory electric field.
 12. Apparatus according toclaim 1, wherein the plurality of electrodes are arranged in atwo-dimensional matrix.
 13. Apparatus according to claim 1, wherein thecontroller selectively electrifies ones of the plurality of electrodesto selectively generate one of two perpendicular electric fields.
 14. Amethod of controlling the output of a gland, comprising: providing atleast one electrode near the gland; and applying a non-excitatoryelectric field to the gland.
 15. A method according to claim 14, whereinthe non-excitatory electric field inhibits the activity of hormoneproducing cells in the gland.
 16. A method according to claim 14,wherein the non-excitatory electric field is a substantially DC field.17. A method according to claim 16, comprising periodically changing thepolarity of the field.
 18. A method according to claim 14, wherein thegland is a pancreas.
 19. A method according to claim 18, furthercomprising monitoring a level of glucose in the blood, wherein applyingthe electric field comprises applying the field responsive to saidmonitored level.
 20. Apparatus for controlling the output of a gland,comprising: a sensor for measuring a level of a chemical in a bloodstream; at least one electrode adjacent said gland; and a controllerwhich electrifies said electrode with a non-excitatory electric field,responsive to the measured level.
 21. Apparatus according to claim 20,wherein the chemical is glucose.
 22. Apparatus according to claim 20,wherein said apparatus is completely implantable.
 23. A method ofcontrolling the activation profile of a gland, comprising: determining adesired activation profile for the gland; and applying at least onenon-excitatory field to a portion of the gland to modify its activationprofile.
 24. A method according to claim 23, wherein applying anelectric field comprises applying the electric field at a delay after alocal activation time
 25. A method according to claim 23, furthercomprising, applying at least one excitatory electric field to thegland.
 26. A method according to claim 23, wherein applying anon-excitatory field comprises applying an inhibitory electric field tothe gland.
 27. A method according to claim 23, wherein applying anon-excitatory field comprises applying an electric field which reduceshormonal secretion in the gland.
 28. A method according to claim 23,wherein applying a non-excitatory field comprises applying an electricfield which increases hormonal secretion in the gland.